title: Clinical implications of discordance between low-density lipoprotein cholesterol and particle number.
abstract: BACKGROUND
  The amount of cholesterol per low-density lipoprotein (LDL) particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals.
  
  
  METHODS
  LDL-P measured by nuclear magnetic resonance spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis, a community-based cohort of 6814 persons free of clinical cardiovascular disease (CVD) at entry and followed for CVD events (n = 319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥ 12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, gender, and race.
  
  
  RESULTS
  LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR 1.20, 95% CI [CI] 1.08-1.34; and 1.32, 95% CI 1.19-1.47, respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR 1.45, 95% CI 1.19-1.78; LDL-C HR 1.07, 95% CI 0.88-1.30). IMT also tracked with LDL-P rather than LDL-C, ie, adjusted mean IMT of 958, 932, and 917 microm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (P = .002) but not LDL-P (P = .60).
  
  
  CONCLUSIONS
  For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.
authors.affiliation: LipoScience, Inc., Raleigh, NC, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
authors.forename: Irina
authors.initials: I
authors.lastname: Shalaurova
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Mackey
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D008078:Cholesterol, LDL / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL